This application seeks support for the continuation of the Diabetes-Endocrinology Center at the University of Chicago. The objectives of the Diabetes Center program include 1) Research in the etiology, pathogenesis, biochemical abnormalities and clinical course of diabetes mellitus; 2) Promotion of interdisciplinary clinical and basic research initiatives; 3) Increase in intramural education activities; 4) Improvement of the care of diabetic patients. The Center's core facilities and lines of communication enhance the effectiveness of all diabetes-related research projects underway at the University, encourage new endeavors, and provide a framework and stimulus for additional collaborative research programs among the investigators of different disciplines and backgrounds. Individual research activities now in progress with support from the Center and its facilities include studies on: Isolation and properties of proglucagon; isolation and characterization of beta cell plasma membranes; isolation and characterization of preproinsulin, isolation of mRNA for proinsulin; studies on the insulin genes; regulation of insulin biosynthesis and secretion; studies on islet cell plasma membranes; lipoprotein lipase and hypertriglyceridemia in diabetes; tissue culture of islet cells and islet cell tumors; the mechanism of conversion of proinsulin; the role of prostaglandins in insulin secretion; insulin binding, degradation and action in hepatocytes; insulin regulation of protein synthesis in muscle; induction of non-ketotic hyperglycemic diabetic coma; CNS control of carbohydrate metabolism; serum proinsulin and C-peptide levels in normal and diabetic subjects; regulation of adipose cell carbohydrate and lipid metabolism; and therapy of diabetic ketoacidosis. BIBLIOGRAPHIC REFERENCES: Rubenstein, A.H., and Steiner, D.F. Islet cell dysfunction. Diabetes Mellitus: Fogarty International Center Series on Preventative Medicine. Vol. 4, chapter 6, pp. 59-72. Stefan S. Fajans, ed. DHEW Publication No. 76-854 (NIH) (1976). Kuzuya, H., Blix, P.M., Horwitz, D.L., Steiner, D.F., and Rubenstein, A.H. Determination of free and total insulin and C-peptide in insulin-treated diabetics. Diabetes, 26, 22-29, (1977).